We have shown: 1) that somatic cell hybrids between normal human diploid fibroblasts and HT 1080-6TG human fibrosarcoma cells behave as transformed cells in vitro and form tumors in nude mice and, 2) that hybrids between HT 1080-6TG human fibrosarcoma cells and primary rodent cells segregate rodent chromosomes and are transformed and malignant independently of the rodent chromosomes that they have retained. Hybrids between phenotypically normal rodent cells derived from established cell lines and HT 1080 cells were found, however, to lose human chromosomes and to segregate into tumorigenic and non-tumorigenic hybrid clones. We propose to study the genetics of malignancy in the HT 1080 human fibrosarcoma cell line and in other human fibrosarcomas. The human chromosome(s) responsible for the expression of the transformed phenotype in vitro and for the malignant behaviour in vivo will be identified by the somatic cell hybridization approach. These studies should indicate whether the gene(s) that allow HT 1080 cells to grow indefinitely in culture and to express the transformed and the malignant phenotypes are the same or are different. We also propose to clone and characterize the human HT 1080 gene responsible for the expression of cell transformation and malignancy by a combination of DNA mediated gene transfer and recombinant DNA technqiues. In addition, we intend to continue our studies on the expression of rodent and human ribosomal RNAs and histones to try to understand the moecular basis of their species specific suppression in rodent-HT 1080 human hybrid cells.